Defensins are cationic antimicrobial peptides and are components of the innate immune system. In humans, the alpha defensins are produced by neutrophils or the Paneth cells of the intestinal tract while the beta defensins are produced by epithelial cells. Defensins have broad spectrum anti-microbial properties against gram negative and gram positive bacteria, some fungi as well as enveloped viruses.
The exact mechanism for the anti-microbial properties is not completely understood but the hydrophobicity and the net positive charge of the peptides appear to be important in its interaction and disruption of the microbial cell wall and cell membrane.
Several studies suggest that full length defensins may form dimers at a bacterial membrane but non-covalent forms (Hoover et al., 2000; Hoover et al., 2001 Schibili at al., 2002) and one study suggests that dimerisation may affect antimicrobial properties (Campopiano et al., 2004). However, the properties of these dimers were not studied or characterised in detail.
The development of antibiotic resistance is a challenge in the development of antibiotics. Although the antimicrobial activity of defensins is not completely understood, the possible mode of action of defensins suggests that microbial resistance may develop very slowly or minimally and the potential of using defensins as antimicrobials is promising. However, defensins are also known to have toxicity to host cells, including mammalian cells which may limit their application as antimicrobials.
It is therefore desirable to develop new peptide derivatives of defensins with high antimicrobial activity and low host cell toxicity.